The function relationship between the onc genes of transforming retorviruses and their cellular prototypes has been facilitated by structural comparisons at the nucleic acid and predicted protein levels. We have determined the complete nucleotide sequence of the chicken protein-ets gene and compared it to the ets gene of E26. E26 is a genetic hybrid with sequences derived from viral structural genes and parts of essential cellular proto-onc genes. The chicken ets gene is present as a single locus with v-ets homologous sequences found in nine regions over 60 kb of genomic DNA. In addition, the cellular gene contains unique 5' and 3' sequences. Thus, the E26 virus demonstrates (1) substitution of viral genes for parts of normal cellular genes, (2) truncation of the gene, and (3) acquisition of non-cellular coding proto-ets sequences. These structural differences may be responsible for the oncogenic potential of this retrovirus. We have previously determined that the mammalian homologs of v-ets are located on difference chromosomes. The mammalian ets-2 genes from man and mouse encode for nearly identical amino acids and are over 90% conserved relative to the chicken ets gene. The ets-2 gene appears to have mitogenic activity upon transfected cells. The human ets- 1 gene product is over 95% identical to the chicken gene from where the virus transduced ets sequences. Alignment of the predicted ets proteins with v-ets suggests that three domains exist. The domain closest to the carboxyl-termini is highly conserved in all genes characterized from species ranging from human to Drosophila. The domain located at the amino-terminal end of ets-2 is less homologous to v-ets. while the ets-1 gene and the v-ets gene are similar in this region. The central domain of v-ets is found to be similar only to that of ets-1, being very divergent in ets-2. Recombinant DNA technology will be used to generate mutants to evaluate the function of these three domains.